1,3-disubstituted benzazepines as neuropeptide YY1 receptor antagonists

A nuclei, have been designed, synthesized, and evaluated for activity. Thro ugh a blind screening we found the compound 1-N-(3-(N'-(tert-butoxycarbonyl )amino)benzyl)-7-methoxy-(3-(3)-methylureido)-2,3,4,5-tetrahydro-1H-1-benza zepin-2-one (9: IC50 = 1.6 mu M). Chemical modifications of 9 gave a potent NPY Y1 antagonist 3-(N-(4-hydroxyphenyl)-N'-methylguanidino)-1-N-(3-(N'-(t ert-butoxycarbonyl)amino)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one ( 14c: IC50 = 43 nM), which had no affinity for NPY Y2 and Y5 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.